Meredith Carpenter and colleagues report a new capture-based method for target enrichment in ancient-DNA sequencing libraries, which is important as these samples often contain <1% endogenous DNA (Am. J. Hum. Genet. doi:10.1016/j.ajhg.2013.10.002, 28 October 2013). Their method, called whole-genome in-solution capture (WISC), relies on the creation of RNA baits, covering the human genome from a modern reference individual, hybridized to the ancient-DNA libraries in solution and pulled down with streptavidin-coated beads. The unbound and largely nonhuman DNA is washed away, and the captured endogenous DNA is eluted and amplified for sequencing. The authors applied the WISC method to 12 human ancient-DNA libraries dating from 1500 BCE to CE 1500. Their capture method showed 6- to 159-fold enrichments of reads mapping to the human genome and 2- to 13-fold enrichments for unique fragments. To identify informative variation for population genetic analyses, they use SNPs overlapping with the 1000 Genomes Project reference panel. They were also able to generate coverage of mitochondrial DNA for five of the samples and tentatively call mitochondrial DNA haplogroups.